1. Field of the Invention
The present invention relates to a novel therapeutic agent for treatment or prevention of liver disease and a novel piperazine derivative.
2. Description of Prior Art
Liver is an organ showing various functions such as detoxication, carbohydrate metabolism, lipid metabolism, protein metabolism, production and secretion of bile, production of blood coagulation factors, control of production of hormones, and storage of various materials employed for constituting a living body such as fat, glycogen, protein and vitamine. These functions of liver may suffer from acute or chronic damages by action of virus, medicaments, toxic material, alcohol, malnutrition, damage of liver circulation system or bile thrombus. Such damages causes various diseases such as virus hepatitis, hepatitis caused by toxicity of medicaments, alcoholic hepatitis, congestive hepatitis, cholangiolitic hepatitis, fatty liver an jaundice. Such diseases may finally cause liver cirrhosis.
Accordingly, studies have been heretofore made for the purpose of finding medicaments for treatment or prevention of liver disease. Based on these studies, a number of therapeutic agents for liver disease have been developed and employed in practice. Representative examples of the known therapeutic agents for liver disease include Malotilate (diisopropyl 1,3-dithiol-2-ylidene malonate), Catergen ((2R,3S)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3,5,7-triol), and Glycyrrhizin (20.beta.-carboxy-11-oxo-30-norolean-12-en-3.beta.-yl-2-O-.beta.-D-glucopy ranuronosyl-.alpha.-D-glucopyranosiduronic acid).
The present inventors have made study on piperazine derivatives and have discovered that specific piperazine derivatives and their pharmaceutically acceptable salts are effective for prevention and/or treatment of liver disease.
There are known a great number of piperazine derivatives. However, there is known no pharmacogical effect of piperazine derivative as therapeutic agent for liver disease, so long as compounds analogous to the specific piperazine derivatives found by the present inventors. For instance, 4-(2-phenylalkyl)-1-piperazine-carbodithio acid and its alkyl ester is disclosed in Acta Pharm. Suecica, 7(1), 7-22 (1970). However, no pharmacological effect for prevention or treatment of liver disease is suggested. Further, 4-(6,7-dihydoxycumarin-8-yl)methyl-1-piperazine-ethanol is disclosed in Zh. Obshch. Khim. 33(3), 793-7 (1966); 4-{2-(3,4-dihydroxyphenyl)-2-oxo}-ethyl-1-piperazine-ethanol is disclosed in Latv. PSR Zinat. Akad. Vestis, kim. Ser., (5), 593-6 (1968); and 4-{2-(3,4-dihydroxyphenyl)-2-oxo}ethyl-1-methylpyperazine is disclosed in Arzneim.-Forsch., 19(10), 1698-1702 (1969). Nevertheless, there is neither disclosure nor suggestion to indicate pharacological effect of the disclosed piperazine derivatives with respect to prevention or treatment of liver disease.